The Effect of γ‐Aminobutyric Acid on Substrate‐Level Phosphorylation in Brain Mitochondria

Abstract: A consequence of the metabolism of γ‐aminobutyric acid (GABA) via the “GABA shunt” should be a decreased rate of substrate‐level phos‐ phorylation of GDP to GTP. 32P1 labeling of nucleotides was, therefore, studied in uncoupled brain mitochondria with α‐ketoglutarate or a‐ketoglutarate + GABA as substrates. The addition of an equimolar amount of GABA resulted in an approximately 50% reduction of the final specific activity of all mitochondrial nucleotides. This effect was completely reversed by aminooxyacetic acid. GABA did not affect the time course of nucleotide labeling. Although delineation of the mechanism involved requires further study, these preliminary results suggest an important modulatory role of GABA in the intermediary metabolism of brain mitochondria.